학술논문
Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib
Document Type
article
Author
Zhou Zhu; Nicholas C. Turner; Sherene Loi; Fabrice André; Miguel Martin; Véronique Diéras; Karen A. Gelmon; Nadia Harbeck; Cathy Zhang; Joan Q. Cao; Zhengming Yan; Dongrui R. Lu; Ping Wei; Todd L. VanArsdale; Paul A. Rejto; Xin Huang; Hope S. Rugo; Sibylle Loibl; Massimo Cristofanilli; Richard S. Finn; Yuan Liu
Source
npj Precision Oncology, Vol 6, Iss 1, Pp 1-10 (2022)
Subject
Language
English
ISSN
2397-768X
Abstract
Abstract While cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including palbociclib, combined with endocrine therapy (ET), are becoming the standard-of-care for hormone receptor–positive/human epidermal growth factor receptor 2‒negative metastatic breast cancer, further mechanistic insights are needed to maximize benefit from the treatment regimen. Herein, we conducted a systematic comparative analysis of gene expression/progression-free survival relationship from two phase 3 trials (PALOMA-2 [first-line] and PALOMA-3 [≥second-line]). In the ET-only arm, there was no inter-therapy line correlation. However, adding palbociclib resulted in concordant biomarkers independent of initial ET responsiveness, with shared sensitivity genes enriched in estrogen response and resistance genes over-represented by mTORC1 signaling and G2/M checkpoint. Biomarker patterns from the combination arm resembled patterns observed in ET in advanced treatment-naive patients, especially patients likely to be endocrine-responsive. Our findings suggest palbociclib may recondition endocrine-resistant tumors to ET, and may guide optimal therapeutic sequencing by partnering CDK4/6 inhibitors with different ETs. Pfizer (NCT01740427; NCT01942135).